ERK1/2 Activities Are Dispensable for Oocyte Growth but Are Required for Meiotic Maturation and Pronuclear Formation in Mouse

Life Sciences Institute, Zhejiang University, Hangzhou 310058, China

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Corresponding author: E-mail address: hyfan@zju.edu.cn (Heng-Yu Fan)

These authors contributed equally to this work.

摘要

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Abstract: Previous studies revealed that extracellular regulated kinase-1 and -2 (ERK1/2) cascade plays pivotal roles in regulating oocyte meiotic cell cycle progression. However, most knowledge about the in vivo function of ERK1/2 in mammalian oocytes was indirectly obtained from analyzing the phenotypes of Mos knockout mice. In this study, we knocked out Erk1 and Erk2 in mouse oocytes as early as the primordial follicle stage using the well-characterized Gdf9-Cre mouse model, and for the first time directly investigated the in vivo function of ERK1/2 in mouse oocytes. In this novel mouse model, we observed that ERK1/2 activities in oocyte are dispensable for primordial follicle maintenance, activation and follicle growth. Different from theMos null oocytes, the ERK1/2-deleted oocytes had well-assembled spindles at metaphase I (MI), extruded polar body-1 (PB1) with normal sizes, and did not undergo a full parthenogenetic activation characterized for pronuclear formation. However, the ovulated ERK1/2-deleted oocytes had poorly-assembled metaphase II (MII) spindles, spontaneously released polar body-2 (PB2), and were arrested at another metaphase called metaphase III (MIII). In addition, ERK1/2 deletion prevented male pronuclear formation after fertilization, and caused female infertility. In conclusion, these results indicate that ERK1/2 activities are required for not only MII-arrest maintenance, but also efficient pronuclear formation in mouse oocytes.
- Oocyte /
- Female reproduction /
- Meiosis /
- ERK1/2 /
- Fertilization
These authors contributed equally to this work.
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参考文献(24)

[1]	Barrett, C.B., Schroetke, R.M., Van der Hoorn, F.A. et al. Mol. Cell. Biol., 10 (1990),pp. 310-315
[2]	Chen, Z., Gibson, T.B., Robinson, F. et al. MAP kinases Chem. Rev., 101 (2001),pp. 2449-2476
[3]	Choi, T., Fukasawa, K., Zhou, R. et al. The Mos/mitogen-activated protein kinase (MAPK) pathway regulates the size and degradation of the first polar body in maturing mouse oocytes Proc. Natl. Acad. Sci. USA, 93 (1996),pp. 7032-7035
[4]	Colledge, W.H., Carlton, M.B., Udy, G.B. et al. Disruption of c-mos causes parthenogenetic development of unfertilized mouse eggs Nature, 370 (1994),pp. 65-68
[5]	Fan, H.Y., Liu, Z., Shimada, M. et al. MAPK3/1 (ERK1/2) in ovarian granulosa cells are essential for female fertility Science, 324 (2009),pp. 938-941
[6]	Fan, H.Y., Sun, Q.Y. Involvement of mitogen-activated protein kinase cascade during oocyte maturation and fertilization in mammals Biol. Reprod., 70 (2004),pp. 535-547
[7]	Fan, H.Y., Tong, C., Lian, L. et al. Characterization of ribosomal S6 protein kinase p90rsk during meiotic maturation and fertilization in pig oocytes: mitogen-activated protein kinase-associated activation and localization Biol. Reprod., 68 (2003),pp. 968-977
[8]	Fan, H.Y., Tong, C., Teng, C.B. et al. Characterization of Polo-like kinase-1 in rat oocytes and early embryos implies its functional roles in the regulation of meiotic maturation, fertilization, and cleavage Mol. Reprod. Dev., 65 (2003),pp. 318-329
[9]	Frank-Vaillant, M., Jessus, C., Ozon, R. et al. Mol. Biol. Cell, 10 (1999),pp. 3279-3288
[10]	Gu, T.P., Guo, F., Yang, H. et al. The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes Nature, 477 (2011),pp. 606-610
[11]	Hashimoto, N., Watanabe, N., Furuta, Y. et al. Parthenogenetic activation of oocytes in c-mos-deficient mice Nature, 370 (1994),pp. 68-71
[12]	Lan, Z.J., Xu, X., Cooney, A.J. Differential oocyte-specific expression of Cre recombinase activity in GDF-9-iCre, Zp3cre, and Msx2Cre transgenic mice Biol. Reprod., 71 (2004),pp. 1469-1474
[13]	Liang, C.G., Su, Y.Q., Fan, H.Y. et al. Mechanisms regulating oocyte meiotic resumption: roles of mitogen-activated protein kinase Mol. Endocrinol., 21 (2007),pp. 2037-2055
[14]	Reddy, P., Shen, L., Ren, C. et al. Activation of Akt (PKB) and suppression of FKHRL1 in mouse and rat oocytes by stem cell factor during follicular activation and development Dev. Biol., 281 (2005),pp. 160-170
[15]	Roy, L.M., Haccard, O., Izumi, T. et al. Oncogene, 12 (1996),pp. 2203-2211
[16]	Schulze, A., Nicke, B., Warne, P.H. et al. The transcriptional response to raf activation is almost completely dependent on mitogen-activated protein kinase kinase activity and shows a major autocrine component Mol. Biol. Cell, 15 (2004),pp. 3450-3463
[17]	Su, Y.Q., Rubinstein, S., Luria, A. et al. Involvement of MEK-mitogen-activated protein kinase pathway in follicle-stimulating hormone-induced but not spontaneous meiotic resumption of mouse oocytes Biol. Reprod., 65 (2001),pp. 358-365
[18]	Su, Y.Q., Wigglesworth, K., Pendola, F.L. et al. Mitogen-activated protein kinase activity in cumulus cells is essential for gonadotropin-induced oocyte meiotic resumption and cumulus expansion in the mouse Endocrinology, 143 (2002),pp. 2221-2232
[19]	Tong, C., Fan, H.Y., Chen, D.Y. et al. Effects of MEK inhibitor U0126 on meiotic progression in mouse oocytes: microtuble organization, asymmetric division and metaphase II arrest Cell Res., 13 (2003),pp. 375-383
[20]	Verlhac, M.H., de Pennart, H., Maro, B. et al. MAP kinase becomes stably activated at metaphase and is associated with microtubule-organizing centers during meiotic maturation of mouse oocytes Dev. Biol., 158 (1993),pp. 330-340
[21]	Verlhac, M.H., Kubiak, J.Z., Clarke, H.J. et al. Microtubule and chromatin behavior follow MAP kinase activity but not MPF activity during meiosis in mouse oocytes Development, 120 (1994),pp. 1017-1025
[22]	Verlhac, M.H., Kubiak, J.Z., Weber, M. et al. Mos is required for MAP kinase activation and is involved in microtubule organization during meiotic maturation in the mouse Development, 122 (1996),pp. 815-822
[23]	Yu, C., Zhang, Y.L., Pan, W.W. et al. CRL4 complex regulates mammalian oocyte survival and reprogramming by activation of TET proteins Science, 342 (2013),pp. 1518-1521
[24]	Zheng, L.P., Huang, J., Zhang, D.L. et al. c-erbB2 and c-myb induce mouse oocyte maturation involving activation of maturation promoting factor DNA Cell Biol., 31 (2012),pp. 164-170